Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?
- Autores
- Ceballos, Maria Paula; Parody, Juan Pablo; Alvarez, María de Luján; Ingaramo, Paola Inés; Carnovale, Cristina Ester; Carrillo, Maria Cristina
- Año de publicación
- 2011
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Wnt/b-catenin pathway is often dysregulated in hepatocellular carcinoma (HCC). Activated b-catenin accumulates in the cytosol and nucleus and forms a nuclear complex with TCF/LEF factors like TCF4. Interferon-a (IFN-a) has recently been recognized to harbor therapeutic potential in prevention and treatment of HCC. Transforming Growth Factor-b1 (TGF-b1) is a mediator of apoptosis, exerting its effects via Smads proteins. One mode of interaction between Wnt/b-catenin and TGF-b1/Smads pathways is the association of Smads with b-catenin/TCF4. In this study we analyzed the effects of IFNa2b and TGF-b1 treatments on Wnt/b-catenin pathway, Smads proteins levels, b-catenin/TCF4/Smads interaction and proliferation and apoptotic death in HepG2/C3A and Huh7 cell lines. IFN-a2b and TGFb1 attenuated Wnt/b-catenin signal by decreasing b-catenin and Frizzled7 receptor proteins contents and the interaction of b-catenin with TCF4. Truncated b-catenin form present in C3A cell line also diminished after treatments. Both cytokines declined Smads proteins and their interaction with TCF4. The overall cellular response to cytokines was the decrease in proliferation and increase in apoptotic death. Treatment with Wnt3a, which elevates b-catenin protein levels, also generated the increment of Smads proteins contents when comparing with untreated cells. In conclusion, IFN-a2b and TGF-b1 proved to be effective as modulators of Wnt/b-catenin pathway in HCC cell lines holding both wild-type and truncated b-catenin. Since the inhibition ofb-catenin/TCF4/Smads complexes formation may have a critical role in slowing down oncogenesis, IFN-a2b and TGF-b1 could be useful as potential treatments in patients with HCC.
Fil: Ceballos, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Ingaramo, Paola Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina - Materia
-
Beta-Catenin
Transforming Growth Factor Beta-1
Interferon-Alfa
Smad Proteins - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/15408
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Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?Ceballos, Maria PaulaParody, Juan PabloAlvarez, María de LujánIngaramo, Paola InésCarnovale, Cristina EsterCarrillo, Maria CristinaBeta-CateninTransforming Growth Factor Beta-1Interferon-AlfaSmad Proteinshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Wnt/b-catenin pathway is often dysregulated in hepatocellular carcinoma (HCC). Activated b-catenin accumulates in the cytosol and nucleus and forms a nuclear complex with TCF/LEF factors like TCF4. Interferon-a (IFN-a) has recently been recognized to harbor therapeutic potential in prevention and treatment of HCC. Transforming Growth Factor-b1 (TGF-b1) is a mediator of apoptosis, exerting its effects via Smads proteins. One mode of interaction between Wnt/b-catenin and TGF-b1/Smads pathways is the association of Smads with b-catenin/TCF4. In this study we analyzed the effects of IFNa2b and TGF-b1 treatments on Wnt/b-catenin pathway, Smads proteins levels, b-catenin/TCF4/Smads interaction and proliferation and apoptotic death in HepG2/C3A and Huh7 cell lines. IFN-a2b and TGFb1 attenuated Wnt/b-catenin signal by decreasing b-catenin and Frizzled7 receptor proteins contents and the interaction of b-catenin with TCF4. Truncated b-catenin form present in C3A cell line also diminished after treatments. Both cytokines declined Smads proteins and their interaction with TCF4. The overall cellular response to cytokines was the decrease in proliferation and increase in apoptotic death. Treatment with Wnt3a, which elevates b-catenin protein levels, also generated the increment of Smads proteins contents when comparing with untreated cells. In conclusion, IFN-a2b and TGF-b1 proved to be effective as modulators of Wnt/b-catenin pathway in HCC cell lines holding both wild-type and truncated b-catenin. Since the inhibition ofb-catenin/TCF4/Smads complexes formation may have a critical role in slowing down oncogenesis, IFN-a2b and TGF-b1 could be useful as potential treatments in patients with HCC.Fil: Ceballos, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Ingaramo, Paola Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaElsevier Inc2011-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15408Ceballos, Maria Paula; Parody, Juan Pablo; Alvarez, María de Luján; Ingaramo, Paola Inés; Carnovale, Cristina Ester; et al.; Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?; Elsevier Inc; Biochemical Pharmacology; 82; 11; 12-2011; 1682-16910006-2952enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2011.08.001info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0006295211006435info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:57:08Zoai:ri.conicet.gov.ar:11336/15408instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:57:09.016CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma? |
title |
Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma? |
spellingShingle |
Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma? Ceballos, Maria Paula Beta-Catenin Transforming Growth Factor Beta-1 Interferon-Alfa Smad Proteins |
title_short |
Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma? |
title_full |
Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma? |
title_fullStr |
Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma? |
title_full_unstemmed |
Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma? |
title_sort |
Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma? |
dc.creator.none.fl_str_mv |
Ceballos, Maria Paula Parody, Juan Pablo Alvarez, María de Luján Ingaramo, Paola Inés Carnovale, Cristina Ester Carrillo, Maria Cristina |
author |
Ceballos, Maria Paula |
author_facet |
Ceballos, Maria Paula Parody, Juan Pablo Alvarez, María de Luján Ingaramo, Paola Inés Carnovale, Cristina Ester Carrillo, Maria Cristina |
author_role |
author |
author2 |
Parody, Juan Pablo Alvarez, María de Luján Ingaramo, Paola Inés Carnovale, Cristina Ester Carrillo, Maria Cristina |
author2_role |
author author author author author |
dc.subject.none.fl_str_mv |
Beta-Catenin Transforming Growth Factor Beta-1 Interferon-Alfa Smad Proteins |
topic |
Beta-Catenin Transforming Growth Factor Beta-1 Interferon-Alfa Smad Proteins |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Wnt/b-catenin pathway is often dysregulated in hepatocellular carcinoma (HCC). Activated b-catenin accumulates in the cytosol and nucleus and forms a nuclear complex with TCF/LEF factors like TCF4. Interferon-a (IFN-a) has recently been recognized to harbor therapeutic potential in prevention and treatment of HCC. Transforming Growth Factor-b1 (TGF-b1) is a mediator of apoptosis, exerting its effects via Smads proteins. One mode of interaction between Wnt/b-catenin and TGF-b1/Smads pathways is the association of Smads with b-catenin/TCF4. In this study we analyzed the effects of IFNa2b and TGF-b1 treatments on Wnt/b-catenin pathway, Smads proteins levels, b-catenin/TCF4/Smads interaction and proliferation and apoptotic death in HepG2/C3A and Huh7 cell lines. IFN-a2b and TGFb1 attenuated Wnt/b-catenin signal by decreasing b-catenin and Frizzled7 receptor proteins contents and the interaction of b-catenin with TCF4. Truncated b-catenin form present in C3A cell line also diminished after treatments. Both cytokines declined Smads proteins and their interaction with TCF4. The overall cellular response to cytokines was the decrease in proliferation and increase in apoptotic death. Treatment with Wnt3a, which elevates b-catenin protein levels, also generated the increment of Smads proteins contents when comparing with untreated cells. In conclusion, IFN-a2b and TGF-b1 proved to be effective as modulators of Wnt/b-catenin pathway in HCC cell lines holding both wild-type and truncated b-catenin. Since the inhibition ofb-catenin/TCF4/Smads complexes formation may have a critical role in slowing down oncogenesis, IFN-a2b and TGF-b1 could be useful as potential treatments in patients with HCC. Fil: Ceballos, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Ingaramo, Paola Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina |
description |
Wnt/b-catenin pathway is often dysregulated in hepatocellular carcinoma (HCC). Activated b-catenin accumulates in the cytosol and nucleus and forms a nuclear complex with TCF/LEF factors like TCF4. Interferon-a (IFN-a) has recently been recognized to harbor therapeutic potential in prevention and treatment of HCC. Transforming Growth Factor-b1 (TGF-b1) is a mediator of apoptosis, exerting its effects via Smads proteins. One mode of interaction between Wnt/b-catenin and TGF-b1/Smads pathways is the association of Smads with b-catenin/TCF4. In this study we analyzed the effects of IFNa2b and TGF-b1 treatments on Wnt/b-catenin pathway, Smads proteins levels, b-catenin/TCF4/Smads interaction and proliferation and apoptotic death in HepG2/C3A and Huh7 cell lines. IFN-a2b and TGFb1 attenuated Wnt/b-catenin signal by decreasing b-catenin and Frizzled7 receptor proteins contents and the interaction of b-catenin with TCF4. Truncated b-catenin form present in C3A cell line also diminished after treatments. Both cytokines declined Smads proteins and their interaction with TCF4. The overall cellular response to cytokines was the decrease in proliferation and increase in apoptotic death. Treatment with Wnt3a, which elevates b-catenin protein levels, also generated the increment of Smads proteins contents when comparing with untreated cells. In conclusion, IFN-a2b and TGF-b1 proved to be effective as modulators of Wnt/b-catenin pathway in HCC cell lines holding both wild-type and truncated b-catenin. Since the inhibition ofb-catenin/TCF4/Smads complexes formation may have a critical role in slowing down oncogenesis, IFN-a2b and TGF-b1 could be useful as potential treatments in patients with HCC. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-12 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/15408 Ceballos, Maria Paula; Parody, Juan Pablo; Alvarez, María de Luján; Ingaramo, Paola Inés; Carnovale, Cristina Ester; et al.; Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?; Elsevier Inc; Biochemical Pharmacology; 82; 11; 12-2011; 1682-1691 0006-2952 |
url |
http://hdl.handle.net/11336/15408 |
identifier_str_mv |
Ceballos, Maria Paula; Parody, Juan Pablo; Alvarez, María de Luján; Ingaramo, Paola Inés; Carnovale, Cristina Ester; et al.; Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?; Elsevier Inc; Biochemical Pharmacology; 82; 11; 12-2011; 1682-1691 0006-2952 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2011.08.001 info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0006295211006435 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier Inc |
publisher.none.fl_str_mv |
Elsevier Inc |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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score |
13.22299 |